Prenatal diagnosis of distal 13q deletion syndrome in a fetus with esophageal atresia: a case report and review of the literature

Abstract

Background: Chromosome 13q deletion syndrome shows variable clinical features related to the different potential breakpoints in chromosome 13q. The severely malformed phenotype is known to be associated with the deletion of a critical region in 13q32. However, esophageal atresia is a rare symptom and the relevant region is unknown. Thus, determining the association between accurate breakpoints and new clinical features is essential.

Case presentation: A 28-year-old Japanese primigravid woman was referred for fetal growth restriction, absence of a gastric bubble, cerebellar hypoplasia, overlapping fingers, and polyhydramnios at 31 weeks gestation. At 38 + 0 weeks, she delivered a 1774 g female infant. The infant presented with isolated esophageal atresia (Gross type A), Dandy-Walker malformation, right microphthalmia, left coloboma, overlapping fingers, pleurocentrum in the thoracic vertebrae, reduced anogenital distance, and hearing loss. Her karyotype was diagnosed as 46,XX,del(13)(q32.1-qter) by amniocentesis, but array comparative genomic hybridization after birth revealed the deletion of 13q31.3-qter. At 48 days after birth, the infant underwent surgery for esophageal atresia and was later discharged from the hospital at 7 months of age.

Conclusion: This case report and the literature reviews supports the previous findings on the pathological roles of haploinsufficiency of the ZIC2/ZIC5 in Dandy-Walker malformation and the EFBN2 haploinsufficiency in eye malformation and hearing loss. Furthermore, the possible involvement of IRS2, COLA1, and COLA2 in eye malformation were identified. This is the first case of 13q deletion syndrome with esophageal atresia (Gross A), but it may be a symptom of VATER/VACTER association (vertebral defects, anorectal malformations, cardiac defects, tracheoesophageal fistula with or without esophageal atresia, renal malformations, and limb defects), as in the previous cases. These symptoms might also be associated with EFBN2 haploinsufficiency, although further research is required.

Keywords: Array comparative genomic hybridization; Esophageal atresia; Prenatal diagnosis.

Fig. 1

Fetal magnetic resonance imaging scans. Sagittal (a) and axial (b) views at 34 weeks of gestation. Arrows indicate the cerebellum

Fig. 2

Chromosomal analyses. a Results of Giemsa banding by amniocentesis. The arrow indicates the abnormal chromosome 13, as del(13)(q32.1). b The result of fluorescent in situ hybridization by amniocentesis. The normal chromosome 13 had both 13q14 (blue) and 13qter (yellow), but no signal indicative of 13qter was detected on the chromosome del(13)(q32.1). c Array CGH analysis reveals the deleted region of 13q31.2–qter (92973314–115097664). The right panel shows an enlarged view of the gene deletion site in the left panel

Fig. 3

Candidate genes are related to the phenotype of the present patient. The red line shows the deleted region of the present patient. The numbers shown in the parentheses are consistent with the reference numbers